BAF(mSWI/SNF)染色质重塑复合物的表观遗传调控对于胚胎发育至关重要。
Epigenetic regulation by BAF (mSWI/SNF) chromatin remodeling complexes is indispensable for embryonic development.
作者信息
Nguyen Huong, Sokpor Godwin, Pham Linh, Rosenbusch Joachim, Stoykova Anastassia, Staiger Jochen F, Tuoc Tran
机构信息
a University Medical Center , Georg-August-University Goettingen , Germany.
b Max-Planck-Institute for Biophysical Chemistry , Goettingen ; Germany.
出版信息
Cell Cycle. 2016 May 18;15(10):1317-24. doi: 10.1080/15384101.2016.1160984. Epub 2016 Mar 17.
The multi-subunit chromatin-remodeling SWI/SNF (known as BAF for Brg/Brm-associated factor) complexes play essential roles in development. Studies have shown that the loss of individual BAF subunits often affects local chromatin structure and specific transcriptional programs. However, we do not fully understand how BAF complexes function in development because no animal mutant had been engineered to lack entire multi-subunit BAF complexes. Importantly, we recently reported that double conditional knock-out (dcKO) of the BAF155 and BAF170 core subunits in mice abolished the presence of the other BAF subunits in the developing cortex. The generated dcKO mutant provides a novel and powerful tool for investigating how entire BAF complexes affect cortical development. Using this model, we found that BAF complexes globally control the key heterochromatin marks, H3K27me2 and -3, by directly modulating the enzymatic activity of the H3K27 demethylases, Utx and Jmjd3. Here, we present further insights into how the scaffolding ability of the BAF155 and BAF170 core subunits maintains the stability of BAF complexes in the forebrain and throughout the embryo during development. Furthermore, we show that the loss of BAF complexes in the above-described model up-regulates H3K27me3 and impairs forebrain development and embryogenesis. These findings improve our understanding of epigenetic mechanisms and their modulation by the chromatin-remodeling SWI/SNF complexes that control embryonic development.
多亚基染色质重塑SWI/SNF(称为与Brg/Brm相关因子的BAF)复合物在发育过程中发挥着重要作用。研究表明,单个BAF亚基的缺失往往会影响局部染色质结构和特定的转录程序。然而,我们尚未完全了解BAF复合物在发育过程中的功能,因为此前没有构建出缺乏完整多亚基BAF复合物的动物突变体。重要的是,我们最近报道,小鼠中BAF155和BAF170核心亚基的双条件敲除(dcKO)消除了发育中的皮质中其他BAF亚基的存在。所产生的dcKO突变体为研究整个BAF复合物如何影响皮质发育提供了一个新颖而强大的工具。利用这个模型,我们发现BAF复合物通过直接调节H3K27去甲基酶Utx和Jmjd3的酶活性,全局控制关键的异染色质标记H3K27me2和 -3。在这里,我们进一步深入探讨了BAF155和BAF170核心亚基的支架能力如何在发育过程中维持前脑和整个胚胎中BAF复合物的稳定性。此外,我们表明,上述模型中BAF复合物的缺失会上调H3K27me3,并损害前脑发育和胚胎发生。这些发现增进了我们对表观遗传机制及其由控制胚胎发育的染色质重塑SWI/SNF复合物进行调控的理解。
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